The present invention is a method and system for introducing therapeutic agents into living beings in a controlled manner which permits such agents to be directed to a particular locality with a high degree of precision. Such therapeutic agents, which may be used to advantage with the system, include chemotherapeutic drugs, genetic material, living cells introduced for transplantation, and other biological therapeutic agents requiring localization to target tissue for optimum effect.
In accordance with the invention, a computer controlled injection needle is employed to inject a therapeutic agent into select target tissue of a patient, for example, a tumor. The tumor is located using one or more scanning modalities capable of distinguishing the target tissue such as plain view X-ray, computerized axial tomography X-ray (CAT scanning), magnetic resonance imaging (MRI scanning), positron emission tomography (PET scanning), and ultrasound scanning. Once the target tissue is located and its borders defined by the imaging modality, location coordinates are generated and assigned with respect to a support structure supporting the patient. A manipulator arm assembly under computer control is used to move and operate the injection needle. A stored program, having user defined parameters and the location coordinate data, then directs the injection needle to a plurality of sites on the patient's body at corresponding insertion depths which result in positioning the tip of the injection needle into the target tissue at various locations. The therapeutic agent is then injected in controlled amounts at each such injection location. In this manner, the agent may be delivered to the target tissue with greater precision than with prior methods so that less of the therapeutic agent is delivered to non-target tissue where its effects may be deleterious.
The present invention may also be employed with therapeutic agents for effecting tissue engineering, that is the selective growth of various cell types within a target tissue of a patient. One such embodiment uses an agent comprising a growth factor or cytokine in conjunction with another agent for creating specificity. A growth factor may then be employed to cause the selective growth of specific living tissue via cellular proliferation without causing the undesired proliferation of other cell types normally responsive to the growth factor. Growth factors which can be used with such method include those of broad specificity such as EGF, PDGF, fibroblast growth factors (FGFs), hepatocyte growth factor (HGF), insulin, insulinlike growth factor (IGF-1), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and macrophage colony stimulating factor (M-CSF). Such method may be useful not only in treating certain disease states where specific cellular proliferation is of value, but also in enhancing the production of animal products such as milk from dairy cattle and various hormones from genetically engineered animals.
In order to produce such a selective growth agent, a specific growth factor or other cytokine is selected which elicits a desired response (eg., cellular proliferation) in a specific target cell of a multicellular organism. Monoclonal antibodies are then produced which have a specific binding affinity for other cells of the organism that also respond to the growth factor, which other cells are referred to herein as non-target cells. Such monoclonal antibodies are directed toward antigenic determinants that are expressed by non-target cells but not by target cells. The monoclonal antibodies are then conjugated with a protein corresponding to the extracellular domain of the growth factor receptor. In order to eliminate the response of the non-target cells to the growth factor, the monoclonal antibody conjugate is administered together with the growth factor by employing the computer controlled injection needle apparatus as described above. The antibody conjugate then binds to the non-target cells and presents a binding site for the growth factor that results in competitive inhibition of the growth factor's binding to the cell's native growth factor receptor. The target cells, on the other hand, are left fully responsive to the growth factor. The method may also be combined with other techniques for causing tissue growth such as electrical stimulation, used presently for promoting bone healing, as well as specific nutrients needed for cell growth.
Another way to effect tissue engineering is to transplant cells into a target tissue. Certain disease states involving organ failure can be successfully treated by replacing only a small proportion of the organ mass with populations of donor cells. Such donor cells (referred to herein as "cellular transplants") are obtained, for example, from a donor organ by mechanical disruption or enzymatic digestion of the parenchyma of the donor organ. Advances in cell culture techniques have made it possible to maintain donor cells, such as hepatocytes, in a viable and functional state in vitro for extended periods of time until they are transplanted into a recipient. Successful transfer of such cellular transplants into animal recipients has recently been demonstrated for both liver cells (See Rhim et al., Science 263, 1149 (1994)) and heart muscle cells (See Soonpaa et al., Science 264, 98 (1994)).
In order to fully realize the advantages of cellular transplantation, the transplant procedure should be performed in a minimally invasive manner without the requirement of a surgical operation. Placement of the cellular transplants into the correct anatomic location, however, is critical if the cellular transplants are to function properly after implantation. The present invention is a system and method for accomplishing such objectives.
In accordance with the present invention, a transplantation tool (which may be, for example, an injection device such as a hypodermic injection needle or a catheter for delivering cellular transplants through an outflow port to an intraductal or other internal body site within which the catheter is disposed) is manipulated by a manipulator or motor-driven catheter under computer control so as to deliver a predetermined amount of a fluid transplant medium containing cellular transplants to a select anatomical area of a patient's body as defined by location coordinates locating the select body area with respect to a structure supporting the patient. In one embodiment of the invention, the transplantation tool is mechanically positioned by a robotic arm operating automatically in accordance with imaging information derived from a scanning system and fed to a computer. In other embodiments, the transplantation tool is positioned manually by an operator while a computer monitors the operation to provide a computer generated indication of when the tool is operatively positioned so as to effect the injection or other delivery of the transplant medium at a selected coordinate location of the body into select body or organ tissue thereof.
It is therefore a primary object of the present invention to provide a system and method for precisely delivering therapeutic agents to a patient at selected anatomical locations.
It is a further object to provide a computerized method and system that enables user designation of selected anatomical locations for cellular transplant delivery via image signals generated by imaging devices which image signals are stored in a computer and displayed to the user.
It is a further object to provide a system and method that automatically delivers cellular transplants to user selected locations under computer control.
Other objects, features, and advantages of the invention will become evident in light of the following detailed description considered in conjunction with the referenced drawings of a preferred exemplary embodiment according to the present invention.